15-65261002-C-A

Variant names:

• chr15-65261002-C-A
• rs1046927190
• NM_001316943.2:c.716G>T
• PARP16 p.Arg239Leu

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001316943.2(PARP16):​c.716G>T​(p.Arg239Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R239Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PARP16 NM_001316943.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.78
• Publications: 0 publications found

Genes affected

PARP16 (HGNC:26040): (poly(ADP-ribose) polymerase family member 16) Enables kinase binding activity; pentosyltransferase activity; and protein serine/threonine kinase activator activity. Involved in several processes, including IRE1-mediated unfolded protein response; positive regulation of protein serine/threonine kinase activity; and protein ADP-ribosylation. Located in endoplasmic reticulum tubular network and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316943.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP16	NM_001316943.2	MANE Select	c.716G>T	p.Arg239Leu	missense	Exon 5 of 6	NP_001303872.1	Q8N5Y8-1
	PARP16	NM_017851.6		c.716G>T	p.Arg239Leu	missense	Exon 5 of 6	NP_060321.3
	PARP16	NM_001316944.2		c.371G>T	p.Arg124Leu	missense	Exon 3 of 4	NP_001303873.1	Q8N5Y8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP16	ENST00000649807.2	MANE Select	c.716G>T	p.Arg239Leu	missense	Exon 5 of 6	ENSP00000496935.1	Q8N5Y8-1
	PARP16	ENST00000261888.10	TSL:1	c.716G>T	p.Arg239Leu	missense	Exon 5 of 6	ENSP00000261888.6	Q8N5Y8-3
	PARP16	ENST00000906476.1		c.833G>T	p.Arg278Leu	missense	Exon 6 of 7	ENSP00000576535.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.72
Mutation Taster		=19/81	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1046927190; hg19: chr15-65553340;